ArticleThe Journal of clinical investigation2010
MAPK phosphatase-3 promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
56 citing papers in PubMed, 96 citations in OpenAlex.
- Taohe Chengqi Decoction Attenuates Cognitive Impairment in Experimental Sepsis-Associated Encephalopathy.CNS neuroscience & therapeutics · 2026Article
- DUSP family phosphatases in cell signaling, inflammation, and chronic diseases.Journal of biomedical science · 2026Review
- Optical Redox Imaging of Breast Cancer NADH Redox Status Associated with PGC1α Gene Expression.Academic radiology · 2026Article
- MAPK Phosphatase-3 Mediates Chronic Endoplasmic Reticulum Stress Promoting Hepatic Gluconeogenesis.International journal of molecular sciences · 2026Article
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- Dual-specificity phosphatase 6 interferes with the repressive activity of forkhead box O1 towards CYP4A11 that mediates lipid accumulation in the liver.Scientific reports · 2026Article
- Identification of a Novel Gene ARNT2 for Osteogenic Differentiation of Mesenchymal Stem Cells.Calcified tissue international · 2025Article
- Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- DUSP6 regulates Notch1 signalling in colorectal cancer.Nature communications · 2024Article
- Quercetin Regulates Lipid Metabolism and Fat Accumulation by Regulating Inflammatory Responses and Glycometabolism Pathways: A Review.Nutrients · 2024Review
- Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning.NPJ biofilms and microbiomes · 2024Article
- Acute Endoplasmic Reticulum Stress Suppresses Hepatic Gluconeogenesis by Stimulating MAPK Phosphatase 3 Degradation.International journal of molecular sciences · 2023Article
- DUSP6 Deficiency Attenuates Neurodegeneration after Global Cerebral Ischemia.International journal of molecular sciences · 2023Article
- New insights into signal transduction pathways in adrenal steroidogenesis: role of mitochondrial fusion, lipid mediators, and MAPK phosphatases.Frontiers in endocrinology · 2023Review
- O-GlycNacylation Remission Retards the Progression of Non-Alcoholic Fatty Liver Disease.Cells · 2022Review
- Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction.Nature communications · 2022Article
- BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH.Nature metabolism · 2022Article
- Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease.Nutrients · 2022Article
- Hepatocentric Leptin Signaling Modulates Gluconeogenesis via MKP-3.Cellular and molecular gastroenterology and hepatology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Insulin resistance results in dysregulated hepatic gluconeogenesis that contributes to obesity-related hyperglycemia and progression of type 2 diabetes mellitus (T2DM). Recent studies show that MAPK phosphatase-3 (MKP-3) promotes gluconeogenic gene transcription in hepatoma cells, but little is known about the physiological role of MKP-3 in vivo. Here, we have shown that expression of MKP-3 is markedly increased in the liver of diet-induced obese mice. Consistent with this, adenovirus-mediated MKP-3 overexpression in lean mice promoted gluconeogenesis and increased fasting blood glucose levels. Conversely, shRNA knockdown of MKP-3 in both lean and obese mice resulted in decreased fasting blood glucose levels. In vitro experiments identified forkhead box O1 (FOXO1) as a substrate for MKP-3. MKP-3-mediated dephosphorylation of FOXO1 at Ser256 promoted its nuclear translocation and subsequent recruitment to the promoters of key gluconeogenic genes. In addition, we showed that PPARγ coactivator-1α (PGC-1α) acted downstream of FOXO1 to mediate MKP-3-induced gluconeogenesis. These data indicate that MKP-3 is an important regulator of hepatic gluconeogenesis in vivo and suggest that inhibition of MKP-3 activity may provide new therapies for T2DM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.